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首页> 外文期刊>The European Journal of Neuroscience >AMPA receptor antagonist LY293558 reverses preproenkephalin mRNA overexpression in the striatum of 6-OHDA-lesioned-rats treated with l-dopa.
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AMPA receptor antagonist LY293558 reverses preproenkephalin mRNA overexpression in the striatum of 6-OHDA-lesioned-rats treated with l-dopa.

机译：AMPA受体拮抗剂LY293558逆转用左旋多巴治疗的6-OHDA损伤大鼠的纹状体中脑啡肽原mRNA的过度表达。

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摘要

Striatal neurons that contain GABA and enkephalin and project to the external segment of the pallidum are thought to be overactive in Parkinson's disease. Furthermore, it has been shown that the appearance of l-dopa-induced dyskinesias is correlated to an increase of preproenkephalin (PPE) mRNA expression and that some antagonists of glutamate receptors can prevent and reverse l-dopa-induced dyskinesias in parkinsonian rats. The aim of this study was therefore to analyse the effect of a systemic treatment with glutamate receptor antagonists, alone or in combination with l-dopa, on the PPE mRNA level in rats with a 6-hydroxydopamine-induced unilateral lesion of the nigrostriatal pathway. In vehicle-treated animals, PPE mRNA levels were markedly increased in the striatum on the lesioned side. Sub-chronic l-dopa treatment, with bi-daily injections for 22 days, induced a further increase in PPE mRNA expression in the denervated striatum. Administration of the AMPA receptor antagonist, LY293558, partially reversed the lesion-induced and l-dopa-induced increases in PPE mRNA expression. However, although the administration of the NMDA receptor antagonist MK801 showed a tendency to decrease this l-dopa induced overexpression, it did not reach significance. This study provides evidence that glutamatergic antagonists, and particularly AMPA antagonists, tend to reverse PPE neurochemical changes at the striatal level induced by l-dopa in hemiparkinsonian rats.
机译：包含GABA和脑啡肽并投射到苍白球外部的纹状体神经元被认为在帕金森氏病中活动过度。此外，已经显示出l-多巴引起的运动障碍的出现与前脑啡肽原（PPE）mRNA表达的增加有关，并且谷氨酸受体的一些拮抗剂可以预防和逆转帕金森氏大鼠中的l-多巴引起的运动障碍。因此，本研究的目的是分析单独或联合左旋多巴的谷氨酸受体拮抗剂的全身治疗对6-羟基多巴胺诱导的黑质纹状体途径单侧病变大鼠PPE mRNA水平的影响。在用媒介物处理的动物中，病变侧纹状体中PPE mRNA水平显着增加。每日两次注射亚慢性左旋多巴治疗22天，导致去神经纹状体中PPE mRNA表达进一步增加。 AMPA受体拮抗剂LY293558的使用可部分逆转病变引起的和L-多巴引起的PPE mRNA表达的增加。然而，尽管NMDA受体拮抗剂MK801的施用显示出减少这种由l-多巴诱导的过表达的趋势，但是它没有达到目的。这项研究提供的证据表明，谷氨酸能拮抗剂，尤其是AMPA拮抗剂，在半帕金森病大鼠中，在l-多巴诱导的纹状体水平上倾向于逆转PPE神经化学变化。

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